1-Chloro-2-fluorobenzene → 6-Chloro-1-(2-chlorophenyl)-1'-methylspiro[indoline-3,4'-piperidine] maleate

HRID 1632856Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][CH2:9][C:10]3([CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]3)[C:5]2=[CH:4][CH:3]=1.[H-].[Na+].[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1F.[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]\[C:30]([OH:32])=[O:31]>CS(C)=O.CCOCC>[C:27]([OH:34])(=[O:33])/[CH:28]=[CH:29]\[C:30]([OH:32])=[O:31].[Cl:1][C:2]1[CH:7]=[C:6]2[N:8]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[Cl:19])[CH2:9][C:10]3([CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]3)[C:5]2=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 45 °C

Procedure

A mixture of 2.4 g of 6-chloro-1'-methylspiro[indoline-3,4'-piperidine], Example 23b, 0.5 g of sodium hydride (99%) and 6 g of 2-chlorofluorobenzene in 25 ml of dimethylsulfoxide is stirred at 45° C. under nitrogen for 1 hour. Thereafter, the mixture is quenched with ice-water before being extracted thrice with ether. The combined ether extracts are successively washed with water, dried and concentrated under vacuum leaving a reddish oil. The oil is passed through an alumina column, ether eluant, and the purified oil, in ether, is converted to its maleic acid salt. The salt is recrystallized from an acetone-ether mixture to provide off-white platelets, mp 172°-173° C. of 6-chloro-1-(2-chlorophenyl)-1'-methylspiro[indoline-3,4'-piperidine] maleate.

Workup

customThereafter, the mixture is quenched with ice-water
extractionbefore being extracted thrice with ether
washThe combined ether extracts are successively washed with water
customdried
concentrationconcentrated under vacuum
customleaving a reddish oil
customThe salt is recrystallized from an acetone-ether mixture

Sources & evidence

ORD record: ord-9f1628305c14498eaf0580b63eca5b69
Source dataset: uspto-grants-1984_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04477667

Reaction notes

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